Organic mercury compounds



carboxylic acids, or aromatic radicals, for example, cinnamic 5 PatentedApr. 12, 1938 (UNITED s rATEs, PATENT OFFICE ORGANIC MERCURY COMPOUNDSCarl N. Andersen, Watertown, Mass, assignor to Lever Brothers Company, acorporation of Maine v v 1 I N0 Drawing. Application December 7, 1934,

r i i 1 Serial No. 756,477

7 Claims. (01. 260-43) The present invention relates to theproducbond-may be substituted by aliphatic radicals, tion' of certainnew organic mercury compounds, for example, angelic acid, and moreparticularly to aromatic mercury salts v v e of substituted andunsubstituted unsaturated CH3CH'C(CH3)COOH It is an object of'myinvention to produce new acid, CBH-ICHICHCOOH; atropie acid, organicmercury compounds useful as 'germicides CH2;C(C6H5) COOH; and for othertherapeutic purposes.

' I have" discovered that if the essential radical a beta benzoylacrylic acldi 10 of an aromatic mercurycompound consisting ofC6H5COCH;CHCOOH 0 f tmqleus to h i mercury is direct" T l 1e aromaticradical itself may be substituted,

y attached is introduced mto an unsaturated for example orthocoumaricacid carboxylic acid, a compound is produced which has extraordinarilyhighpotency as an antiseptic OHCBHiCHiCHCOOH- and germieide, and at theSame time is eheree- In addition are included triple bond compounds 15terized by relatively low toxicity and other desir- Such a i h cid andits homologues and able prope its substituted derivatives.

The compounds I ave D ep be In my applications, Serial Nos. 694,198 andscribed vas having e general formula RH -Ri, 694,199, filed October 18,1933, I have shown that n Which R rep-resents aromatic structure, to thearomatic mercury radical may be united with 20 a carbon atom of which ee c y iS directly an organic acid by replacing the hydrogen of theattached; and i Which 1 is represents a radical COOH group with thearomatic mercury radical. corresponding to an unsaturated carboxylicacid Th general th d may b used in preparing which is li ked to t RHg upthrough the the above described compounds. In preparing 5 Placement 0fthe hydrogen atom of the COOH these compounds I find that all theunsaturated -D- acids act similarly in that the multiple bond or Mor p ca y R r pr s ts an aromatic the substituted radicals are not disturbed.It is structure, which may be an aromatic nucleus only t H of th 1001-1group which reacts Wit Without Side and the expression under theconditions set forth. The aromatic aromatic structure used-herein isintended to r ry compound is preferably a hydroxide and 30 be genericand include an aromatic nucleus with th h of t reaction is one f orWithout s de c T e aromatic Structure trali'zation to form a salt andwater. As pointed is of t e yp in which none f the uc r out in the abovementioned applications a soluble side chain carbonatoms has directlinkage with lt, such a the acetat may be used when the any elementother than hydrogen, Carbon 0 aromatic mercury compound formed isrelatively 35 mer ury- R y stand for the p yl up. insoluble as comparedwith any of the other CsHs, or for an aromatic hydrocarbon hav compoundsinvolved in the reaction. nucleus similar to p e y oca bo as I haveinvestigated many of the compounds of for example," polycyclic yd o inch the above named class'and a sufficient number to 40 all of thenuclear carbon atoms, other than'the lead me to believe thatsubstantially all of the 40 one atta e 0 y, and y Side Chain unsaturatedacids of the above identified group carbon atoms, have their valencessatisfied either can be employed to produce my novel mercury by carbonor hydrogen. Examples are the (11- compounds, and that the compounds soprepared phenyl', toly Xy y1, and nepthyl roups: have, in greater orlesser, but always in rela- Th unsaturated eerbexylicecid p n in tivelyhigh degree, desirable antiseptic and 40 to the radical R1, moreparticula yists of germicidal properties. I therefore regard my inanunsaturated monobasic aliphatic acid and its vention as generic to andincluding the entire substituted derivatives. It includes acids in abovedefined class. which the substituted radicals are either aromatic Thecompounds may be prepared in various or aliphatic. Examples of .theunsubstituted ways. The following specific examples are given-50 acidsare acrylic 'acid, CHztCHCOOH, and its as illustrative of the methodswhich may be emhomologues, for example, crotonic acid, ployed inproducing my novel compounds, and as illustrative of representativeorganic mercury CH3CHCH'COOH' unsaturated salts falling within the scopeof my The hydrogen on one. or both sides of the doublev invention. 55

Example 1 17.64 grams of phenylmercury hydroxide are dissolved in 4liters of water and heated until solution is complete. The solution isfiltered to remove any gum or insoluble material. To the filtrate areadded 9.76 grams of cinnamic acid dissolved in 400-cc.of 50% alcohol.Aprecipitate results. The mixture is set aside to cool and theprecipitate then filtered and washed Well with warm water and dried. Thecompound is phen ylmercury cinnamate and melts at 178 C.

Example 2 8.82 grams of phenylmercury hydrorddeare'dis solved in 2liters of water and heated until solution is complete. move anyinsoluble material:

cc. of alcohol. A white crystalline precipitate separates and uponconcentration of the solution more white' crystals separate. Themixture-is filtered and the precipitate is Washed Well with warm water,and-dried. It is'recrystallized from alcohol and melts at 68-69 C. It isthe compound phenylmercury atropate.

. Example 3 17.64 grams of phenylmercuryhydroxide: are dissolved'in2'liters of water and heated until sold; tionis complete. The solutionis thenfiltered to remove. any insoluble material. To the"filtrate areadded.12.12 grams of beta-benzoyl acrylicacid. A yellowish precipitatefirst results, but whemthe mixture is allowed to stand a whitecrystalline mass separates. The mixture is filtered, andlthe precipitatewashed well with warm water and alcohol, and dried. It has a meltingpoint of 139-141 C. The compound is phenylm'ercury beta-benzoylacrylate.

Example 5 8.82 grams of phenylmercury hydroxide arefdis solved in 4liters of water and'heated until"solu"- tion is complete. The solutionis filteredto r'e move any, insoluble material. To" the filtrate areadded 30.96 grams. of 90% methyl acrylate'diis solved in 50% methylalcohol. The mixtureis' refluxed for one hour and the solution thenfconcentrated to one-half its original volume. Crys tals separate onstanding and are recovered by filtration, washed well with warm waterandia few-cc. of alcohol, and dried. The materiall'isa white-solid andmelts at 1l8-120C. It.i's--the compound phenylmercury acrylate. Inthis-example the ester, methyl acrylate, is hydrolizedf to yield methylalcohol and acrylicacid. Theacid reacts with-the hydroxide to form thephenyl-' mercury. salt.

The reacting materials: are employed ins-sub-- stantially theoreticalquantities. In some instances, if desired, 10% excess of the acid-may.

The solution is filtered to re- To the 'filtrateiare added 4.88 grams ofatropic acid dissolved in*50' be used in order to assure the completeconversion of the phenylmercury compound.

Any suitable solvent in which the reacting components are soluble may beused as the medium for carrying out the reaction. If they are bothsoluble in water this is generally used for reasons of convenience, butif not other solvents such as the alcohols, acetone ormixtu'r'e's ofthese with each other or" with water, may be employed.

The process may be carried out at any temperattire, for example, roomtemperature.

art how other members of the above identified group may be reacted withan aromatic mercury compound to produce mercury compounds of analogousstructure.

All of the compoundsproduced as above described. are characterized-by.extraordinarily: high po'tencyas' germicides Tests to? determme 'theirefficacy 'in killing :3. -typhosus and staphe aure'us were carried onunder the following conditions:

Aqueous solutions of varying dilutions:- from 1 10,000 upward untilkilling: ceased, were made up.

These dilutions w'ere employed in the condiict or the tests by, theiollowing methods:

Circular 198; U. S. Dept. of AgricuItur-e;:. Dec: 1931, ,describedsasF." D.- A;, method against -Eber thellw typhi (typhoid: bacillus) at: 37C.- and F. D; A. special' method against StaIphsaureus at=37-"C.

Asillustrative ofthepotency of the compounds; the killing power of thefollowing compounds' ls given merely as illustrative.

The figures represent the maximum dilutions at which killing 'llI15minutes resulted.

' st aphr Big M08113 mum,

Phenylmereury beta-benzo'yl acrylate 1:120, 000' i 1550;000Plienylmercury ortho-coumarate 1:50, 000 l:25,000

In additionto-their high germicidal value,:.all of these I compounds arecharacterized by relatively low toxicity. Because of these properties itis possible to use them in'extreme dilutions and in many situationswhere known germicides; because of toxic or other undesired properties;cannot be employed. They maybe used-externally and locally; and insomecases administered internally with. satisfactory results from thegermicidal standpointand without harmful effect to the. body. or itsfunctions- The compounds-retain their germicidal activ ity" whenincorporated in soap and-various menstruumsi employed :in preparing.germicid-aLwom positions."

When these: new compounds" are to be used directly as germicidestheysmay'rbe employedin aqueous orother "solutions on they. may. beformed into various preparations such as mouth'wa'shes; toothpastes,soaps, ointments, etc'.

I claim:

l. A'n'ew organic compound of the general for mula -R;Hg='.R1, in whichR-represents an' aroinatic structure-to acarbon'atom' of whichthe-mercury is directly attached" and in which' none' of the car-- bonatoms has direct linkage with any elements other than hydrogen, carbonand mercury; and in which m-represen-ts the radicalor amunsamment of thehydrogen atom of the COOH group.

2. A new organic compound of the general formula RHg.R1, in which Rrepresents an aromatic structure to a carbon atom of which the mercuryis directly attached and in which none of the carbon atoms has directlinkage with any elements other than hydrogen, carbon and mercury; andin which R1 represents an aromatic substi tuted unsaturated aliphaticacid radical to which the RI-Ig group is linked by the replacement ofthe hydrogen atom of the COOH group.

3. A new organic compound of the general formula CsH5Hg.R1, in which R1represents the radical of an unsaturated acid comprising an unsaturatedacyclic linkage and containing a carboxyl group, to which radical theCsHsHg group is linked by the replacement of the hydrogen atom of theCOOH group.

4 A new organic compound of the general formula C6H5Hg.R1, in which R1represents an aromatic substituted unsaturated aliphatic acid radical towhich the CeHaHg group is linked by the replacement of the hydrogen atomof the COOH group.

5. Phenylmercury cinnamate.

6. Phenylmercury atropate. v

'7. Phenylmercury ortho-coumarate.

CARL N. ANDERSEN.

